Case-control Study of the Frequency of Thrombophilic Disorders in Couples with Late Foetal Loss and no Thrombotic Antecedent
Case-control Study of the Frequency of Thrombophilic Disorders in Couples with Late Foetal Loss and no Thrombotic Antecedent
复制标题
晚期流产且无血栓前因的夫妇中血栓形成倾向疾病频率的病例对照研究
作者：
J. Gris;I. Quéré;Françoise Monpeyrou;É. Mercier;S. Ripart;M. Tailland;M. Hoffet;Jacques Berlan;J. Daurès;P. Marés
背景：患有家族性血栓病的妇女死产的风险增加。我们假设静脉血栓形成的无症状危险因素的存在可能是晚期胎儿丢失的危险因素。方法：我们进行了一项病例对照研究，研究遗传性血栓性缺陷、抗磷脂相关标记物和亚甲基四氢叶酸还原酶（MTHFR）基因C677T突变在至少一次晚期不明原因胎儿丢失患者和成功妊娠的对照妇女中的患病率。病例和对照的伴侣也进行了研究。书面结论的病理检查的胎盘，当可用时，也进行了审查。结果：我们发现21.1%的患者和3.9%的对照组至少存在一种静脉血栓形成的阳性生物学危险因素（p < 10-4）。在女性中，与静脉血栓形成的任何阳性生物学危险因素相关的死产的粗优势比为5.5,95%可信区间（95% ci）[3.4-9.0]。病例伴侣和对照组之间无差异（5.2%和4.7%）。采用条件logistic回归分析，仍存在蛋白S缺乏、抗β2糖蛋白I IgG抗体阳性、抗心磷脂IgG抗体阳性、V Leiden因子突变4个调整后的死产危险因素。MTHFR基因中的C677T突变不是个体危险因素，但纯合子基因型与前4种危险因素密切相关（16.8%的患者对0.9%的对照组）。在有这种关联的妇女中，死产总是发生在怀孕期间没有补充叶酸的情况下。现有的胎盘病理分析结论发现，与阴性标记的患者相比，至少有一种血栓栓塞风险标记阳性的患者，特别是与C677T MTHFR纯合基因型相关的患者，“胎盘母血管病”的比例非常高（p < 10-4）。结论：胎盘血栓形成导致的晚期胎儿丢失，有时可能是母体多因子血栓形成前状态的结果，该状态将传统的遗传性或获得性血栓形成危险因素与易患急性轻度高同型半胱氨酸血症的条件联系起来（遗传易感性与妊娠后期叶酸需求增加共存）。
Summary Background: Women with familial thrombophilia have an increased risk of still birth. We postulated that the presence of asymptomatic risk factors for venous thrombosis might be a risk factor for late foetal loss. Methods: We performed a case-control study on the prevalence of heritable thrombophilic defects, of antiphospholipid-related markers and of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with at least one episode of late unexplained foetal loss and in control women with successful pregnancies. Partners of cases and controls were also studied. Written conclusions of the pathological examination of the placentas, when available, were also reviewed. Results: We found at least one positive biological risk factor for venous thrombosis in 21.1% of the patients and in 3.9% of the controls (p <10–4). In women, the crude odds ratio for still birth associated with any positive biological risk factor for venous thrombosis was 5.5, 95% confidence interval (95%CI) [3.4-9.0]. No difference was found between partners of cases and controls (5.2% and 4.7%). Using conditional logistic regression analysis, 4 adjusted risk factors for still birth remained: protein S deficiency, positive anti β2 glycoprotein I IgG antibodies, positive anticardiolipin IgG antibodies and the factor V Leiden mutation. The C677T mutation in the MTHFR gene was not an individual risk factor but an homozygous genotype was strongly associated with the former 4 risk factors (16.8% of patients vs. 0.9% of controls). In women with such associations, still births always occurred in absence of folic acid supplementation during pregnancy. Available conclusions of pathological analysis of placentas were found to have a very high proportion of “maternal vascular disease of the placenta” in patients with at least one positive risk marker for thromboembolism, specially in case of association with the C677T MTHFR homozygous genotype, compared to patients with negative markers (p <10–4). Conclusions: Late foetal loss, through placenta thrombosis, may sometimes be the consequence of a maternal multifactorial prothrombotic state associating traditional heritable or acquired thrombosis risk factors to conditions predisposing to an acute mild hyperhomocysteinaemia (coexistence of a genetic predisposition with late pregnancy-related increased folate needs).
影响因子：
20.3
作者：
P. Comp;G. R. Thurnau;J. Welsh;C. T. Esmon
通讯作者：
P. Comp;G. R. Thurnau;J. Welsh;C. T. Esmon
DOI：
10.1073/pnas.92.3.850
发表时间：
1995-01-31
影响因子：
11.1
作者：
HEALY, AM;RAYBURN, HB;WEILER, H
通讯作者：
WEILER, H